Pain Pathways - DPT Notes

Learning Objectives

  • Compare and contrast acute and chronic pain
  • Compare and contrast nociceptive and neuropathic pain
  • Define structures and terms of the pain pathways
  • Compare and contrast myelinated A delta and unmyelinated C fibers
  • Define dermatomes and their role in pain evaluation
  • Explain transmission of pain impulse from the periphery to the spinal cord
  • Explain efferent response to pain impulses
  • Explain pain transmission along the ascending pathway from spinal cord to brain
  • Explain how the descending pathway modulates pain transmission
  • Describe the role of the substantia gelatinosa and lamina I in the dorsal horn
  • Describe the role of areas of the brain in pain perception ◦ Thalamus, hypothalamus, PAG, RVM, RAS
  • Describe the role of the endogenous opioid system
  • Describe the PT implications for understanding the descending modulatory pain pathway

What is Pain?

  • According to the International Association for the Study of Pain (IASP), pain is an unpleasant sensory and emotional experience that is associated with or resembles actual or potential tissue damage
  • Pain can be:
    • Sharp or dull, or other sensations like stinging, burning, aching, tingling, and other adjectives
    • Constant or intermittent
    • Localized to one more areas, or be felt all over
  • Net effect of a complex interaction of the ascending and descending nervous systems involving biochemical, physiologic, psychological, and neocortical processes

How Pain is Classified?

  • Basis Types of Pain
    • Duration
      • Acute
      • Chronic
    • Acute on chronic
    • Cause
      • Cancer
      • Non-cancer
    • Mechanism
      • Nociceptive (physiological)
      • Neuropathic (pathological)

Acute vs Chronic Pain

  • Acute pain: caused by noxious stimulation due to injury, disease process, or abnormal function of muscle or viscera
    • Somatic:
      • Superficial: skin, subQ
        • cuts, burns
      • Deep: muscles/bone
        • fracture, arthritis
    • Visceral
      • From viscera (organs)
        • angina, UTI, peptic ulcer
      • Referred pain
        • Pain perceived at site different from its point of origin by innervated by same spinal segment
        • Ex: MI pain in left arm, neck, chest
  • Chronic pain: extends 3-6 months beyond onset or beyond expected healing period
    • May be nociceptive, inflammatory, neuropathic, or functional in origin
    • Distinguishing feature: psychological mechanisms or environmental factors play a major role

Acute vs Chronic Pain

  • Acute Pain
    • Onset & Timing
      • Sudden, short duration
      • Resolves/disappears when tissue heals
    • Signal
      • Warning sign of actual or potential tissue damage
    • Severity
      • Correlates with amount of damage
    • CNS involvement
      • CNS intact- acute pain is a symptom
    • Psychological effects
      • Less, but unrelieved pain can lead to anxiety and sleeplessness (improves when pain relieved)
  • Chronic Pain
    • Onset & Timing
      • Insidious onset
      • Pain persists despite tissue healing
    • Signal
      • Not a warning signal of damage
      • False alarm
    • Severity
      • Severity not correlated with damage
    • CNS involvement
      • CNS may be dysfunctional
      • Chronic pain is a disease
    • Psychological effects
      • Often associated with depression, anger, fear, social withdrawal, etc.

Mechanism of Pain

  • NOCICEPTIVE PAIN
    • Pain that occurs in response to tissue damage/injury
    • Can be well localized when it comes from soft tissue; less localized coming from viscera
  • NEUROPATHIC PAIN
    • Pain caused by lesion or disease of the PNS or CNS
    • Nerve damage/persistent stimulation results in rewiring of pain circuits
    • Causes spontaneous nerve stimulation, autonomic neuronal stimulation, increased discharge of dorsal horn neurons

Nociceptive Pain vs Neuropathic Pain

  • Nociceptive Pain
    • Well localized
    • Sharp
    • Worse with movement
    • Obvious tissue injury or disease
    • Inflammation
    • Physiological pain
  • Neuropathic Pain
    • Not well localized
    • Burning
    • Shooting
    • Numbness
    • Pins and needles
    • Tissue injury may not be obvious
    • Nerve injury
    • Changes in wiring
    • Abnormal firing
    • Loss of modulation
    • Pathological pain

Terms and Structures of the Pain Pathways

  • Nociceptors: free sensory nerve endings present in most tissues of the body
    • Thermal: extremes of temperature
    • Chemical: acids or compounds produced in the body. Examples: bradykinin, histamine, or prostaglandin
    • Mechanical/physical: pressure
  • Pain threshold: refers to the level of stimulation required to activate the nerve ending sufficiently for the individual to perceive pain
  • Pain tolerance: refers to the ability to withstand pain or the perception of its intensity

Structures of the Pain Pathways

  • First-order neuron (aka, dorsal root ganglion): neurons that receive impulse from the skin and proprioceptors and send it to the spinal cord
  • Second-order neuron: located in dorsal horn, 1st order synapse with these neurons to send impulse up the SC to the thalamus and cerebellum
  • Third-order neuron: pick up neural impulse from the thalamus and carry it on to the somatosensory portion of the cerebral cortex

Structures of the Pain Pathways

  • Superficial lamina I and substantia gelatinosa (lamina II) are where modulation of pain-related info first occurs
  • Substantia gelatinosa: grey matter structure, responsible for relaying pain, temperature, and light touch sensation to the brain
    • Serves as a major synaptic site between first- and second-order neurons with an abundant population of interneurons modulating communication
    • Notable for high concentration of substance P, enkephalins, endorphins, dynorphins, and corresponding receptors

Afferent Fibers Conduct Pain Impulses

  • Myelinated A delta fibers transmit impulses rapidly
  • Unmyelinated C fibers that transmit impulses slowly
  • Acute pain is transmitted by A delta fibers
    • sudden, sharp, localized pain related to thermal and physical stimuli primarily from skin and mucous membranes
  • Chronic pain is transmitted by C fibers
    • C fibers receive thermal, physical, and chemical stimuli from muscle, tendons, the myocardium, and the digestive tract as well as from the skin
    • often experienced as a diffuse, dull, burning or aching sensation

Dermatomes

  • Each spinal nerve conducts impulses from a specific area of the skin called a dermatome
  • The somatosensory cortex is “mapped” to correspond to areas of the body so that the brain can interpret the source of the pain
  • Dermatomes can be used to test for areas of sensory loss or pain sensation and thus determine the site of damage after spinal cord injuries

Efferent Fibers Respond to Pain Impulse

  • Reflex at spinal cord responds to pain signal
  • Results in motor (efferent) impulse back to muscle
  • Initiates involuntary muscle contraction to move body away from pain source

Ascending Pathways

  • Spinothalamic bundle
    • neospinothalamic tract: fast impulses for acute sharp pain
    • paleospinothalamic tract: slower impulses for chronic or dull pain
  • Double pathway explains the two stages of pain one often experiences with an injury to the skin: the initial sharp severe pain, followed by a duller but persistent throbbing or aching pain
  • Spinothalamic tracts connect with reticular formation in the brain, hypothalamus, thalamus and other structures
  • Ascends to the somatosensory area of the parietal lobe in cerebral cortex

Descending Pathways

  • Descending pain modulatory system is triggered once pain signal has reached cortex
  • GOAL: modulate pain signal though neuronal inhibition to allow an organism to function enough to respond to pain source
    • “Top down” pain modulation
  • Periaqueductal gray (PAG) receives pain info via spinomescencephalic tract
  • Relays it to the rostral ventral medulla (RVM) where signal sent down spinal cord
  • This activates the endogenous opiate system to suppress pain

Areas of the brain that play a role in pain relay and perception

  • Reticular activating system (RAS): influence brain’s awareness of incoming pain stimuli
    • Drugs can depress RAS and decrease pain perception/experience
  • Hypothalamus: impacts pain response through connection with pituitary glands and SNS
  • Thalamus: serves as a relay center and processes nociceptive info before transmitting it to various parts of the cortex
  • Periaqueductal gray (PAG): midbrain structure plays key role in pain modulation; inhibits and facilitate pain perception with connections to the thalamus, RVM, and dorsal horn
  • Rostral ventral medulla (RVM): brainstem structure made up of made up of the nucleus raphe magnus, the nucleus gigantocellularis pars alpha (GiA), and the adjacent reticular formation. It modifies ascending signal reaching the brain as well as modulating descending signals. *The PAG-RVM pathway is one of the best-studied circuits in the descending pain modulation system. Its activation facilitates and inhibits pain.

Endogenous Opioid System

  • 3 types of opioids and opioid receptors to regulate neurotransmission of pain signals
    • Β-endorphins – which predominately binds to mu opioid receptors
    • Dynorphins – which predominately bind to kappa opioid receptors
    • Enkephalins – which predominately bind to delta opioid receptors
  • Activation leads to a reduction in neurotransmitter release and cell hyperpolarization, reducing cell excitability
  • Opioids can regulate pain on several levels, both within the spinal cord, brain stem, and cortex
  • Opioid receptors located in brain (thalamus, PAG, RVM), spinal cord (dorsal horn), and peripheral organs
    • Analgesic effects mediated via mu receptors

Where are Opioid Receptors?

  • In dorsal horn
    • the post-synaptic ends of second-order neurons have opioid receptors within the membrane.
    • Pre-synaptic ends where first-order neurons contain opioid receptors
  • Highest densities of opioid receptors in the brain:
    • thalamus
    • midbrain periaqueductal gray
    • rostral ventromedial medulla

Implications for Physical Therapists

  • Knowledge of the descending pain modulatory system and its components can help PTs in several ways:
    • It helps PTs explain why the amount of pain a patient is experiencing does not always relate to the amount of tissue damage they have sustained
      • Educate patients about the role of the descending pain modulatory system
      • More on Pain Science in Weeks 4 and 5
    • Knowledge of the anatomy involved in the descending pain modulatory system can help physiotherapists utilize management strategies to that access and activate the system
      • Adding distractions to exercises and performing exercises in different emotional states and/or in different environments
    • Manual techniques (eg joint mobilizations, manipulations) have been proposed to activate the system and significantly contribute to their therapeutic effects